Can an otorhinolaryngological visit induce the suspect of allergic rhinitis in children?

Summary: Allergic rhinitis (AR) is very frequent in childhood. AR is commonly associated with some co-morbidities and typical clinical features. This study aimed to test the hypothesis whether an otorhinolaryngological (ORL) visit could induce the suspect of AR. Globally, 1,002 children (550 males, mean age 5.77 years) were consecutively visited at an ORL clinic. Clinical visit, nasal endoscopy, and skin prick test were performed in all patients. In particular, history investigated atopic familiarity, birth, feeding type, passive smoking, comorbidities, including asthma, respiratory infections, otitis media, respiratory sleep disorder. Endoscopy assessed the tonsil and adenoid volume, turbinate contacts, mucosal color, and nasal discharge. Univariate and multivariate analysis were performed. The study showed that 547 (54.6%) children had AR. Some parameters were predicting factor for suspecting AR: middle turbinate contact (OR = 9.27), familial atopy (OR = 6.24), pale nasal mucosa (OR = 4.95), large adenoid volume (OR = 3.02 for score 4), and asthma co-morbidity (OR = 2.95). In conclusion this real-life study showed that during an ORL visit it is possible to suspect AR in children with turbinate hypertrophy, familial atopy, nasal pale mucosa, adenoid enlargement, and asthma comorbidity.

Low-dose multicomponent medication modulates humoral and cellular immune response in an ex-vivo study on children subjected to adenoid surgery.

Respiratory infections, mainly in children, are a demanding challenge for physicians. Commonly, a relative immune-defect sustains their recurrence. At present, there is no standardized treatment for their prevention acting on the immune system. Citomix is a low-dose multicomponent medication largely used in this issue. The current study evaluated its ex vivo effect on adenoidal mononuclear cells recovered from children operated for adenoid hypertrophy. B cell phenotype, and IFN-γ, IL-6, IL-10, IgG, IgA, IgM in culture supernatants were evaluated. Citomix was able to significantly increase the expression of B memory cells, IFN-γ, IL-6, IgA and IgM, and significantly decrease IL-10 and IgG. The current outcomes could be consistent with a strategy deputed to improve the early immune response to pathogens. In conclusion, the present ex vivo study suggests that Citomix might be a promising medication in preventing and early treating respiratory infections.

Predicting the effect of treatment in paediatric OSA by clinical examination and functional respiratory imaging.

OBJECTIVE: The aim of this study was to investigate whether functional respiratory imaging (FRI) or clinical examination could predict treatment outcome for obstructive sleep apnea (OSA) in normal-weight, non-syndromic children. METHODS: Normal weight children diagnosed with OSA by polysomnography were prospectively included. All children got a thorough evaluation and an ultra-low dose computed tomography scan of the upper airway (UA). A 3-D reconstruction was built combined with computational fluid dynamics for FRI. Decisions on the need and type of surgery were based upon findings during drug-induced sleep endoscopy. A second polysomnography was performed 3-12 months after surgery. RESULTS: Ninety-one children were included: 62 boys, 5.0 ± 2.7 years, and BMI z-score of -0.1 ± 1.2. Children with more severe OSA had a smaller volume of the overlap region between the adenoids and tonsils. Nineteen out of 60 patients had persistent OSA (oAHI >2/h). A lower conductance in the UA and a higher tonsil score predicted successful treatment. CONCLUSIONS: A less constricted airway, as characterized by both FRI and a lower tonsil score, was associated with a less favorable response to (adeno) tonsillectomy. Further studies after treatment using FRI and DISE are warranted to further characterize the UA of these subjects.

Bases neurales de la toma de decisiones / Neural substrates of decision-making

Introducción: La toma de decisiones (TD) puede definirse como la selección de una alternativa dentro de un rango de opciones existentes, considerando los posibles resultados de las selecciones realizadas y sus consecuencias en el comportamiento presente y futuro. Tradicionalmente, se ha afirmado que desde el punto de vista anatómico la base neural fundamental de este proceso lo constituye la corteza prefrontal (CPF); sin embargo, nuevos estudios validan la hipótesis de la existencia una compleja red neural que incluyen estructuras tanto corticales como subcorticales. Objetivo: La presente revisión tiene como objetivo resumir la evidencia sobre las bases anatómicas relacionadas con el proceso de toma de decisiones tomando en consideración la información disponible hasta la actualidad, que valida la existencia de una compleja red neural que sirve de soporte a este complejo proceso neuropsicológico. Desarrollo: La evidencia contemporánea indica que dentro de las bases neurales de la TD se encuentran regiones de la CPF como la corteza orbitofrontal, dorsolateral y el giro cingulado anterior. Además, el proceso es asistido por regiones subcorticales, como la amígdala, el hipocampo y el cerebelo. Conclusiones: Los resultados hasta el momento demuestran la importancia de las estructuras corticales y subcorticales en la toma de decisiones. Las bases neurales de la TD consisten en una compleja red neural con conexiones cortico-corticales y cortico-subcorticales, que incluyen tanto las subdivisiones de la CPF como las estructuras límbicas y el cerebelo

Introduction: Decision-making is the process of selecting a course of action from among 2 or more alternatives by considering the potential outcomes of selecting each option and estimating its consequences in the short, medium and long term. The prefrontal cortex (PFC) has traditionally been considered the key neural structure in decision-making process. However, new studies support the hypothesis that describes a complex neural network including both cortical and subcortical structures. Objective: The aim of this review is to summarise evidence on the anatomical structures underlying the decision-making process, considering new findings that support the existence of a complex neural network that gives rise to this complex neuropsychological process. Development: Current evidence shows that the cortical structures involved in decision-making include the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). This process is assisted by subcortical structures including the amygdala, thalamus, and cerebellum. Conclusions: Findings to date show that both cortical and subcortical brain regions contribute to the decision-making process. The neural basis of decision-making is a complex neural network of cortico-cortical and cortico-subcortical connections which includes subareas of the PFC, limbic structures, and the cerebellum

A pro-inflammatory role for nuclear factor kappa B in childhood obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Childhood obstructive sleep apnea syndrome (OSAS) is associated with an elevation of inflammatory markers such as C-reactive protein (CRP) that correlates with specific morbidities and subsides following intervention. In adults, OSAS is associated with activation of the transcription factor nuclear factor kappa B (NF-kB). We explored the mechanisms underlying NF-kB activation, based on the hypothesis that specific NF-kB signaling is activated in children with OSAS. DESIGN: Adenoid and tonsillar tissues from children with OSAS and matched controls were immunostained against NF-kB classical (p65 and p50) and alternative (RelB and p52) pathway subunits, and NF-kB-dependent cytokines: interleukin (IL)- 1α, IL-1ß, tumor necrosis factor-α, and IL-8). Serum CRP levels were measured in all subjects. NF-kB induction was evaluated by a luciferase-NF-kB reporter assay in L428 cells constitutively expressing NF-kB and in Jurkat cells with inducible NF-kB expression. p65 translocation to the nucleus, reflecting NF-kB activation, was measured in cells expressing fluorescent NF-kB-p65-GFP (green fluorescent protein). SETTING: Sleep research laboratory. PATIENTS OR PARTICIPANTS: Twenty-five children with OSAS and 24 without OSAS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Higher expression of IL-1α and classical NF-kB subunits p65 and p50 was observed in adenoids and tonsils of children with OSAS. Patient serum induced NF-kB activity, as measured by a luciferase-NF-kB reporter assay and by induction of p65 nuclear translocation in cells permanently transfected with GFP-p65 plasmid. IL-1ß showed increased epithelial expression in OSAS tissues. CONCLUSIONS: Nuclear factor kappa B is locally and systemically activated in children with obstructive sleep apnea syndrome. This observation may motivate the search for new anti-inflammatory strategies for controlling nuclear factor kappa B activation in obstructive sleep apnea syndrome.

Adenoids during childhood: the facts.

Adenoids are constantly exposed to viral and bacterial agents as well as to allergens. They play a major role in the upper airways immunity, being effector organs in both mucosal-type and systemic-type adaptive immunity. Because of both their immunological function and their specific location, adenoids are considered to be as reservoirs of viruses and bacteria. Reiterative infections may therefore contribute both to Eustachian tube dysfunction and to tissue hypertrophy. Nasal endoscopy is a key diagnostic tool to detect both adenoid hypertrophy and adenoiditis. Moreover, such a procedure may be very helpful in detecting bacterial biofilms that could justify the concomitant presence of recurrent episodes of otitis media, chronic and occult sinusitis in children. Even though the connection between allergies and adenoidal diseases is not completely clear, allergic diseases cause an inflammatory state that influences adenoidal tissue as well, configuring the picture of allergic adenoiditis, a condition in which adenoid tissue exhibit numerous IgE positive mast cells. Several studies are still needed to better understand the relationship between allergies and infections and the influence they play on adenoids during childhood.

Which obese children should have a sleep study?

BACKGROUND: The UK government has recommended the development of obesity services for children. As obesity is common, studying every obese child for obstructive sleep apnoea (OSA) would be challenging and full paediatric sleep services are not available in every area in Europe. The purpose of this study was to consider how well clinical features predict significant OSA in obese children in order to help prioritise the need for sleep studies and subsequent treatment. METHODS: Consecutive children referred for obesity management aged 2-16 years with a body mass index (BMI) of >2.5 z scores for age were offered a sleep study using overnight oximetry and audiovisual recordings. Significant OSA was defined as > or = 5 dips/h of >4% oxygen saturation or > or = 5 respiratory-event related arousals/h. RESULTS: Forty-one of 158 (26%) children (mean BMI z score 3.7) had significant OSA and 95% of these had either reported apnoea, restless sleep or tonsillar hypertrophy (TH). Nineteen percent of all children had none of these features. BMI was not related to OSA. CONCLUSION: If only obese children with reported apnoea, restless sleep or TH have a sleep study, 95% of all obese children with significant OSA will be identified using this method.

[Apoptosis lymphocytes T and B in adenoid]. / Apoptoza limfocytów T i B w migdalku gardlowym.

Apoptosis is a physiological form of cell death, which plays an important role in embryogenesis, cellular homeostasis, tissue atrophy and removal of tumor and mutated cells. Apoptosis of T and B lymphocytes is a fundamental process regulating antigen receptor selection during T cell maturation and homeostasis of the immune system. It also plays a key role in elimination of autoreactive lymphocytes. There are two major signaling pathways of apoptosis: the death receptor pathway and intrinsic pathway the mitochondrial pathway.

Uptake of microparticles into the epithelium of human nasopharyngeal lymphoid tissue.

The M cells of nasopharyngeal lymphoid tissue (NALT) have been considered to play an important role for vaccine delivery systems in humans. A number of investigations have reported particle uptake data in NALT of rodents. However, there have been no reports indicating any involvement of the nasopharyngeal lymphoid tissue in human vaccination. In the present study, we investigated whether the epithelium of human adenoid tissues might incorporate fluorescent microparticles using electron and fluorescent microscopy. The dissected adenoid tissues were incubated with various sizes and concentrations of fluorescent microparticles for 120 min at 37 degrees C. Furthermore, the effect of surface coatings of microparticles with cations on the uptake into the epithelium of adenoid tissues was investigated. Transmission electron microscopy revealed that microparticles were taken up by the M cells of human nasopharyngeal lymphoid tissues. The NALT-M cells showed greater uptake of the smallest particles, 0.2 microm in diameter, than those of 0.5, 1.0, or 2.0 microm diameter. It was also revealed that surface coatings with poly-L: -lysin or chitosan resulted in efficient uptake into the NALT. These results indicate that nasal administration of antigenic microparticles, which were coated with cationic materials, probably leads to a useful method of transnasal vaccination against respiratory and intestinal infections in humans.

Human nasopharyngeal-associated lymphoreticular tissues. Functional analysis of subepithelial and intraepithelial B and T cells from adenoids and tonsils.

Subepithelial and intraepithelial lymphocytes of human adenoids and tonsils were characterized and directly compared to determine the potential contribution of these tissues to mucosal and systemic immune responses. The distribution of T and B cell subsets, cytokine patterns, and antibody (Ab) isotype profiles were similar for adenoids and tonsils. Both tissues contained predominantly B cells ( approximately 65%), approximately 5% macrophages, and 30% CD3(+) T cells. The T cells were primarily of the CD4(+) subset ( approximately 80%). Tonsillar intraepithelial lymphocytes were also enriched in B cells. The analysis of dispersed cells revealed a higher frequency of cells secreting IgG than IgA and the predominant Ig subclass profiles were IgG1 > IgG3 and IgA1 > IgA2, respectively. In situ analysis also revealed higher numbers of IgG- than IgA-positive cells. These IgG-positive cells were present in the epithelium and in the subepithelial zones of both tonsils and adenoids. Mitogen-triggered T cells from tonsils and adenoids produced both Th1- and Th2-type cytokines, clearly exhibiting their pluripotentiality for support of cell-mediated and Ab responses. Interestingly, antigen-specific T cells produced interferon-gamma and lower levels of interleukin-5. These results suggest that adenoids and tonsils of the nasopharyngeal-associated lymphoreticular tissues represent a distinct component of the mucosal-associated lymphoreticular tissues with features of both systemic and mucosal compartments.

Effects on the ciliated epithelium of protein D-producing and -nonproducing nontypeable Haemophilus influenzae in nasopharyngeal tissue cultures.

A pair of isogenic, nontypeable Haemophilus influenzae strains, one expressing protein D and the other protein D-negative, was compared in their ability to cause damage in a human nasopharyngeal tissue culture model. Damage was assessed by measuring the ciliary beat frequency (CBF) of tissue specimens at 12 h intervals. Cultures inoculated with H. influenzae manifested a decrease in CBF beginning after 12 h, with a maximum decrease after 36 h. The impairment of ciliary function by the protein D-expressing strain was significantly greater than that caused by the protein D-negative mutant (P<.01). Tissue specimens examined by scanning and transmission electron microscopy after 24 h appeared normal. After 48 h of incubation, the protein D-expressing strain caused a significant loss of cilia. These findings suggest that protein D is involved in the pathogenesis of upper respiratory tract infections due to nontypeable H. influenzae, probably by enhancing functional and morphological damage to cilia.

Signal transduction pathways in modulation of ciliary beat frequency by methacholine.

The release of endogenous neurotransmitters plays an important role in the airway mucosal defense system. We studied the in vitro effect of methacholine, a beta-methyl ester of acetylcholine, on the ciliary beat frequency (CBF) of human adenoid explants and its mechanism of action. Tissue explants were cultured at 35 degrees C and covered with 1.0 mL of culture medium: minimum essential Eagle's medium (MEM) containing L-arginine (1.2 x 10(-3) mol/L). Methacholine was added to the cultured tissue at concentrations of 10(-10), 10(-8), and 10(-6) mol/L. The CBF was determined by phase contrast microscopy and microphotometry. Methacholine increased CBF in a dose-dependent manner with a maximum increase of 23.0% +/- 1.8% (p < .001). Atropine (10(-6) mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p < .0007). The role of endogenous prostaglandins in methacholine-induced ciliostimulation was determined by treating specimens with a cyclooxygenase inhibitor (diclofenac sodium). Diclofenac (10(-6) mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p < .0007). To determine if nitric oxide (NO) acts as an intermediary in ciliostimulation by methacholine, endogenous NO production was inhibited by treating specimens with an L-arginine analog, NG-nitro-L-arginine methyl ester (L-NAME), prior to addition of methacholine. L-NAME (10(-6) mol/L) inhibited the effects of methacholine in L-arginine-free MEM (p < .008), and this inhibition was reversed by L-arginine (10(-3) mol/L). To further examine the actions of NO in methacholine-induced ciliostimulation, a cyclic guanosine 3'5'-monophosphate (cGMP) kinase inhibitor (KT-5823) was used, prior to the addition of methacholine. KT-5823 (10(-6) mol/L) significantly inhibited the effects of methacholine (p < .0001). Ciliostimulation by methacholine in human upper airway mucosa involves both prostaglandin and NO second messengers and activation of a cGMP-dependent kinase.

Dual signal transduction mechanisms modulate ciliary beat frequency in upper airway epithelium.

This study investigated the effects of methacholine and terbutaline on the ciliary beat frequency (CBF) of upper airway epithelium. The CBF of cultured human adenoid explants was measured using microphotometry. Methacholine (10(-6) M) and terbutaline (10(-6)M) increased CBF a maximum of 23.0 +/- 1.8% (P < 0.001) and 16.5 +/- 2.3% (P < 0.001). Inhibition of endogenous nitric oxide (NO) production by nitro-L-arginine methyl ester (L-NAME) (10(-6) M) abolished the effects of methacholine in L-arginine-free medium (P < 0.008). This inhibition was reversed by addition of L-arginine. There was no inhibition of terbutaline-induced ciliostimulation by L-NAME (P < 0.5). KT-5823 (10(-6)M), a guanosine 3',5'-cyclic monophosphate (cGMP) kinase inhibitor, significantly inhibited the effects of methacholine (P < 0.0001), but not terbutaline (P > 0.15). H-89 (10(-6) M), a cAMP kinase inhibitor, significantly inhibited terbutaline-induced ciliostimulation (P < 0.0001), but not methacholine-induced ciliostimulation (P > 0.05). Diclofenac (10(-6) M), a cyclooxygenase inhibitor, significantly inhibited the effects of methacholine (P < 0.0007) but had no effect on terbutaline-induced ciliostimulation (P > 0.05). These findings suggest that the CBF of upper airway epithelium is modulated through at least two distinct pathways. The beta 2-adrenoceptor produces ciliary stimulation by a pathway involving increased intracellular cAMP levels, while the muscarinic receptor increases CBF by a mechanism involving production of prostaglandins, NO, and cGMP.

The functional role of the adenoids in speech.

Illustrative cases are presented showing a variety of interrelationships between the adenoids and the activity of the velopharyngeal valve in speech. The cases presented were selected from a group of 1000 patients referred because of suspected velopharyngeal diseases. When appropriate, complete velopharyngeal assessment was made including otolaryngological speech and hearing examination, polysomnography, nasendoscopy, multiview videofluoroscopy and cephalometry. New observations are described which further elucidate the mechanism by which the adenoids may change the mechanism of velopharyngeal valving and consequently speech patterns. In conclusion, procedures involving the adenoids and tonsils and surgical correction of velopharyngeal valve abnormalities to improve respiratory function must be performed in a manner which ensures preservation of normal speech activity. Similarly, surgical correction of velopharyngeal valve abnormalities to improve speech activity must preserve its respiratory function. The velopharyngeal valve and the adeno-tonsils must be considered together whenever diagnosis and a therapeutic intervention of either of them is considered. A clinical method for patient evaluation, patient management and the development of a rational therapeutic approach is presented.

Effects of prostaglandins D2 and E2 on ciliary beat frequency of human upper respiratory cilia in vitro.

Diminished mucociliary transport can occur in a type-I (Ig-E mediated) allergic reaction. We determined the effects of the allergy mediators prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) on the ciliary beat frequency (CBF) of human upper respiratory cilia in vitro. Human adenoid tissue was used as the source for ciliated epithelium. CBF was measured by a computerized photo-electric method. PGD2 (10(-8)-10(-5) M, n = 7) showed no statistically significant effect on CBF. PGE2 (10(-9)-10(-6) M, n = 10) caused a significant dose-dependent stimulation, with a maximum of 37% (ANOVA, p < 0.001). Thus prostaglandins D2 and E2 do not exert a direct negative influence on ciliary activity, which could account for a decrease in mucociliary transport. The stimulating effect of PGE2 may be relevant in promoting mucociliary clearance in vivo.

Histamine and leukotriene C4 effects on in vitro ciliary beat frequency of human upper respiratory cilia.

Decreased mucociliary transport can occur in patients with type I (IgE-mediated) allergic rhinitis or allergic asthma. This study investigated if the allergic mediators histamine and leukotriene C4 (LTC4) could interfere with ciliary beat frequency (CBF) of in vitro human upper respiratory cilia and eventually result in decreased mucociliary transport. Ciliated epithelium of human adenoid tissue was used in the experiments and CBF was determined using a computer-assisted photoelectric method. Histamine in concentrations of 10(-6) - 10(-3) M (n = 12) and LTC4 as 10(-9) - 10(-6) M solutions (n = 10) showed no statistically significant dose-dependent effect on CBF in vitro.